CA2736361C - Combinaison d'un inhibiteur de la phosphatidylinositol-3-kinase (pi3k) et d'un inhibiteur de mtor - Google Patents

Combinaison d'un inhibiteur de la phosphatidylinositol-3-kinase (pi3k) et d'un inhibiteur de mtor Download PDF

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Publication number: CA2736361C
Authority: CA; Canada
Prior art keywords: treatment; pharmaceutically acceptable; acceptable salt; mtor; combination
Prior art date: 2008-10-31
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Fee Related

Application number

CA2736361A

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English (en)

Other versions

CA2736361A1 (fr

Inventor

Carlos Garcia-Echeverria

Sauveur-Michel Maira

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Novartis AG

Original Assignee

Novartis AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2008-10-31

Filing date

2009-10-29

Publication date

2017-10-10

2009-10-29 Application filed by Novartis AG filed Critical Novartis AG

2010-05-06 Publication of CA2736361A1 publication Critical patent/CA2736361A1/fr

2017-10-10 Application granted granted Critical

2017-10-10 Publication of CA2736361C publication Critical patent/CA2736361C/fr

Status Expired - Fee Related legal-status Critical Current

2029-10-29 Anticipated expiration legal-status Critical

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CA2736361A 2008-10-31 2009-10-29 Combinaison d'un inhibiteur de la phosphatidylinositol-3-kinase (pi3k) et d'un inhibiteur de mtor Expired - Fee Related CA2736361C (fr)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP08168044.9		2008-10-31
EP08168044		2008-10-31
PCT/EP2009/064274 WO2010049481A1 (fr)	2008-10-31	2009-10-29	Combinaison d’un inhibiteur de la phosphatidylinositol-3-kinase (pi3k) et d’un inhibiteur de mtor

Publications (2)

Publication Number	Publication Date
CA2736361A1 CA2736361A1 (fr)	2010-05-06
CA2736361C true CA2736361C (fr)	2017-10-10

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CA2736361A Expired - Fee Related CA2736361C (fr)	2008-10-31	2009-10-29	Combinaison d'un inhibiteur de la phosphatidylinositol-3-kinase (pi3k) et d'un inhibiteur de mtor

Country Status (12)

Country	Link
US (3)	US20110195966A1 (fr)
EP (1)	EP2349275B1 (fr)
JP (4)	JP2012506898A (fr)
KR (1)	KR20110090911A (fr)
CN (2)	CN105030784A (fr)
AU (1)	AU2009309616B2 (fr)
BR (1)	BRPI0921802A8 (fr)
CA (1)	CA2736361C (fr)
ES (1)	ES2627677T3 (fr)
MX (1)	MX2011004585A (fr)
RU (2)	RU2538683C2 (fr)
WO (1)	WO2010049481A1 (fr)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US20100048524A1 (en)	2008-03-14	2010-02-25	Angela Brodie	Novel C-17-Heteroaryl Steroidal CYP17 Inhibitors/Antiandrogens;Synthesis In Vitro Biological Activities, Pharmacokinetics and Antitumor Activity
US8476431B2 (en) *	2008-11-03	2013-07-02	Itellikine LLC	Benzoxazole kinase inhibitors and methods of use
CA2937492C (fr)	2008-11-11	2019-08-13	The Board Of Regents Of The University Of Texas System	Inhibition de cible mammalienne de rapamycine
EP2393827B1 (fr)	2009-02-05	2015-10-07	Tokai Pharmaceuticals, Inc.	Nouveaux promédicaments à base d'inhibiteurs cyp17 stéroïdiens/anti-androgènes
US9283211B1 (en)	2009-11-11	2016-03-15	Rapamycin Holdings, Llc	Oral rapamycin preparation and use for stomatitis
US10391059B2 (en)	2009-11-11	2019-08-27	Rapamycin Holdings, Inc.	Oral rapamycin nanoparticle preparations and use
GB2478556A (en) *	2010-03-09	2011-09-14	Myrovlytis Technology Ventures Ltd	A composition for use in the treatment of Birt-Hogg-Dubô sydrome
CN103391780B (zh) *	2011-02-16	2015-08-19	诺瓦提斯公司	用于治疗神经变性疾病的治疗剂的组合物
TWI592411B (zh) *	2011-02-23	2017-07-21	英特爾立秦有限責任公司	激酶抑制劑之組合及其用途
KR20130131461A (ko) *	2011-03-07	2013-12-03	폰다지오네 텔레톤	Tfeb 변종 및 그의 용도
WO2012148846A1 (fr) *	2011-04-25	2012-11-01	Novartis Ag	Association d'un inhibiteur de phosphatidylinositol-3-kinase (pi3k) et d'un inhibiteur de mtor
JP6047149B2 (ja) *	2011-05-04	2016-12-21	インテリカイン，エルエルシー	併用の医薬組成物およびその使用
MX342326B (es)	2011-09-27	2016-09-26	Novartis Ag	3-pirimidin-4-il-oxazolidin-2-onas como inhibidoras de idh mutante.
CN104080786A (zh) *	2011-11-08	2014-10-01	因特利凯有限责任公司	使用多种药剂的治疗方案
US9174994B2 (en)	2011-11-23	2015-11-03	Intellikine, Llc	Enhanced treatment regimens using mTor inhibitors
UY34632A (es) *	2012-02-24	2013-05-31	Novartis Ag	Compuestos de oxazolidin- 2- ona y usos de los mismos
RU2012112128A (ru) *	2012-03-29	2013-10-10	Холин Максим Николаевич	ИНГИБИТОРЫ СИГНАЛЬНОГО ПУТИ PI3K/AKT/IKK/NF-kB, ИХ ФАРМАЦЕВТИЧЕСКИ ПРИЕМЛЕМЫЕ СОЛИ И СОДЕРЖАЩИЕ ИХ КОМПОЗИЦИИ ДЛЯ ПРОФИЛАКТИКИ И ЛЕЧЕНИЯ ВИРУСНЫХ ЗАБОЛЕВАНИЙ
US9296733B2 (en)	2012-11-12	2016-03-29	Novartis Ag	Oxazolidin-2-one-pyrimidine derivative and use thereof for the treatment of conditions, diseases and disorders dependent upon PI3 kinases
US20160030401A1 (en)	2013-03-13	2016-02-04	The Board Of Regents Of The University Of Texas System	Use of mtor inhibitors for prevention of intestinal polyp growth and cancer
CA2904170A1 (fr)	2013-03-14	2014-09-25	University Of Maryland, Baltimore	Agents de diminution du recepteur des androgenes et leurs utilisations
CA2903979A1 (fr)	2013-03-14	2014-09-18	Novartis Ag	3-pyrimidin-4-yl-oxazolidin-2-ones comme inhibiteurs d'idh mutante
HK1214533A1 (zh)	2013-03-15	2016-07-29	基因泰克公司	治疗癌症和预防癌症耐药性的方法
TWI710558B (zh) *	2013-05-01	2020-11-21	瑞士商赫孚孟拉羅股份公司	二雜芳基化合物及其用途
KR20160058774A (ko)	2013-08-12	2016-05-25	토카이 파마슈티컬, 아이엔씨.	안드로겐-표적 치료제를 이용하는 종양 질환 치료를 위한 바이오마커
CN103483345B (zh) *	2013-09-25	2016-07-06	中山大学	Pi3k激酶抑制剂、包含其的药物组合物及其应用
US9700544B2 (en)	2013-12-31	2017-07-11	Neal K Vail	Oral rapamycin nanoparticle preparations
EP3283127B1 (fr) *	2015-04-15	2020-02-26	University of Massachusetts	Compositions et procédés utilisables en vue de la réactivation de chromosomes xi
US10576076B2 (en)	2015-05-20	2020-03-03	Novartis Ag	Pharmaceutical combination of everolimus with dactolisib
JP2020500930A (ja)	2016-11-23	2020-01-16	ノバルティスアーゲー	エベロリムス、ダクトリシブまたは両方で免疫応答を増強する方法
WO2019157516A1 (fr)	2018-02-12	2019-08-15	resTORbio, Inc.	Polythérapies
KR20210158019A (ko)	2020-06-23	2021-12-30	주식회사 온코빅스	포스파티딜이노시톨 3-키나제(pi3k) 억제제로써 pten 과오종 증후군에 의한 종양 세포의 성장 또는 증식을 억제하는데 유용한 신규한 피리미딘 유도체 및 이의 약제학적으로 허용가능한 염, 및 이를 유효성분으로 함유하는 약제학적 조성물
CN112294967A (zh) *	2020-09-30	2021-02-02	四川大学	一种mTOR抑制剂与抗癌药物的用途

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
KR100919266B1 (ko) *	2000-06-26	2009-09-30	엔벤타 바이오파마슈티컬스 코포레이션	인간 파필로마 바이러스 치료법
TW200626610A (en) *	2004-10-13	2006-08-01	Wyeth Corp	Analogs of 17-hydroxywortmannin as PI3K inhibitors
CN101222925A (zh) *	2005-07-20	2008-07-16	诺瓦提斯公司	嘧啶基氨基苯甲酰胺和mTOR激酶抑制剂的组合产品
KR101464384B1 (ko) *	2005-11-22	2014-11-21	쿠도스 파마슈티칼스 리미티드	ｍＴＯＲ 억제제로서 피리도피리미딘, 피라조피리미딘 및피리미도피리미딘 유도체
JO2660B1 (en) *	2006-01-20	2012-06-17	نوفارتيس ايه جي	Pi-3 inhibitors and methods of use
EP1981890A2 (fr) *	2006-01-25	2008-10-22	OSI Pharmaceuticals, Inc.	INHIBITEURS DE mTOR INSATURES
WO2007120897A2 (fr) *	2006-04-13	2007-10-25	The Trustees Of Columbia University In The City Of New York	Compositions et dispositifs intraluminaux permettant d'inhiber la stenose vasculaire
CA2675558A1 (fr) *	2007-02-06	2008-08-14	Novartis Ag	Inhibiteurs de la pi3-kinase et procedes de leur utilisation
RU2478387C2 (ru) *	2007-02-20	2013-04-10	Новартис Аг	ИМИДАЗОХИНОЛИНЫ В КАЧЕСТВЕ ДВОЙНЫХ ИНГИБИТОРОВ ЛИПИДКИНАЗЫ И mTOR
AU2008335469A1 (en) *	2007-12-13	2009-06-18	Novartis Ag	Combinations of therapeutic agents for treating cancer

2009
- 2009-10-29 CA CA2736361A patent/CA2736361C/fr not_active Expired - Fee Related
- 2009-10-29 WO PCT/EP2009/064274 patent/WO2010049481A1/fr not_active Ceased
- 2009-10-29 EP EP09744391.5A patent/EP2349275B1/fr not_active Not-in-force
- 2009-10-29 RU RU2011121508/15A patent/RU2538683C2/ru not_active IP Right Cessation
- 2009-10-29 MX MX2011004585A patent/MX2011004585A/es active IP Right Grant
- 2009-10-29 BR BRPI0921802A patent/BRPI0921802A8/pt not_active IP Right Cessation
- 2009-10-29 CN CN201510402018.9A patent/CN105030784A/zh active Pending
- 2009-10-29 JP JP2011533721A patent/JP2012506898A/ja not_active Withdrawn
- 2009-10-29 CN CN2009801431736A patent/CN102202668A/zh active Pending
- 2009-10-29 KR KR1020117009771A patent/KR20110090911A/ko not_active Ceased
- 2009-10-29 AU AU2009309616A patent/AU2009309616B2/en not_active Ceased
- 2009-10-29 ES ES09744391.5T patent/ES2627677T3/es active Active
- 2009-10-29 US US13/123,956 patent/US20110195966A1/en not_active Abandoned
2014
- 2014-04-15 RU RU2014115188/15A patent/RU2014115188A/ru not_active Application Discontinuation
- 2014-09-05 JP JP2014181069A patent/JP2015013883A/ja not_active Withdrawn
2015
- 2015-11-24 US US14/950,869 patent/US20160136175A1/en not_active Abandoned
2016
- 2016-07-06 JP JP2016134514A patent/JP2017002058A/ja not_active Ceased
2018
- 2018-01-16 US US15/872,043 patent/US20180133226A1/en not_active Abandoned
- 2018-07-20 JP JP2018136756A patent/JP2018197243A/ja active Pending

Also Published As

Publication number	Publication date
CN105030784A (zh)	2015-11-11
JP2018197243A (ja)	2018-12-13
AU2009309616A2 (en)	2011-07-07
RU2538683C2 (ru)	2015-01-10
WO2010049481A1 (fr)	2010-05-06
EP2349275A1 (fr)	2011-08-03
JP2012506898A (ja)	2012-03-22
MX2011004585A (es)	2011-06-01
AU2009309616A1 (en)	2010-05-06
JP2017002058A (ja)	2017-01-05
ES2627677T3 (es)	2017-07-31
BRPI0921802A8 (pt)	2018-03-13
RU2014115188A (ru)	2015-10-20
AU2009309616B2 (en)	2014-02-13
JP2015013883A (ja)	2015-01-22
US20160136175A1 (en)	2016-05-19
CA2736361A1 (fr)	2010-05-06
KR20110090911A (ko)	2011-08-10
US20110195966A1 (en)	2011-08-11
US20180133226A1 (en)	2018-05-17
BRPI0921802A2 (pt)	2016-09-27
RU2011121508A (ru)	2012-12-10
CN102202668A (zh)	2011-09-28
EP2349275B1 (fr)	2017-03-08

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Date	Code	Title	Description
2014-11-04	EEER	Examination request	Effective date: 20141023
2020-12-10	MKLA	Lapsed	Effective date: 20201029

Publication	Publication Date	Title
AU2009309616B2 (en)	2014-02-13	Combination of a phosphatidylinositol-3-kinase (PI3K) inhibitor and a mTOR inhibitor
HUE031367T2 (en)	2017-07-28	A pharmaceutical combination comprising an Hsp 90 inhibitor and a mTOR inhibitor
AU2016202372B2 (en)	2017-07-20	Combination of a phosphatidylinositol-3-kinase (PI3K) inhibitor and a mTOR inhibitor
AU2008202690A1 (en)	2008-07-10	Antineoplastic combination
AU2005312061B2 (en)	2009-09-03	Combinations comprising epothilones and protein tyrosine kinase inhibitors and pharmaceutical uses thereof
CN102834094B (zh)	2015-05-06	有机化合物的组合产品及其制药用途
KR20130087058A (ko)	2013-08-05	피리미딜아미노벤즈아미드와 ｍｔｏｒ 키나제 억제제의 조합물
HK1226654A (en)	2017-10-06	Anti-tumor activity of temsirolimus in papillary renal cell cancer
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HK1142538A (en)	2010-12-10	Anti-tumor activity of temsirolimus in papillary renal cell cancer